1. Field of the Invention
Phosphine ligands play a critical role in organic and organometallic chemistry and find important application as ancillary phosphine ligands attached to transition metals. Important chemical processes rely on chiral phosphine ligands to carry out asymmetric hydrogenation, isomerization and related reactions. These reactions lead to new products, some of which are chiral and represent new and exciting medicines and drugs useful in the pharmaceutical industry.
Until now, the vast majority of available phosphine ligands useful in these catalytic processes were aryl phosphines. The reason for the use of aryl substituents in the prior art was, in addition to their reasonable effectiveness, their availability. On the other hand, the prior art methods of synthesizing phosphine ligands containing alkyl substituents is very difficult and inefficient. However, the last few years have evidenced a growing interest in phosphine ligands containing alkyl substituents. This interest has been spurred by the growing belief that the use of alkyl substituents, of which cyclohexyl is a prime example, provide an environment wherein catalytic processes for obtaining chiral type products is enhanced.
As stated above, there are processes to produce cycloalkyl phosphines. However, these processes are complex and thus produce cycloalkyl phosphines in low yield and low purity. Thus, a process for the production of cycloalkyl phosphines, particularly cyclohexyl phosphines, in high yield and high purity, is a need well recognized in the art.
2. Background of the Prior Art
Processes to make asymmetrical phosphines and diphosphines which are useful in forming complexes with transition metals having optically active coordinating groups are known in the art. U.S. Pat. No. 4,010,181 to Aviron-Violet provides a process for making diphosphines, in which the phosphorus atoms are linked to a cycloalkyl group, by contacting a sulfonic acid ester of a stereoisomer of trans-bis-(1,2-hydroxymethyl)-cyclobutene with an alkali metal phosphide. The synthesis of these reactant involve difficult preparation schemes. The product of this process is recited to be useful as a ligand in the formation of rhodium complexes which act as catalysts in the hydrogenation of substituted acrylic acids and acid esters to produce optically active propionic acid derivatives.
U.S. Pat. No. 4,216,331 to Henderson, Jr. describes a chiral bisphosphine-rhodium complex which complex acts as a catalyst for the asymmetrical reduction of a tetramisole precursor leading to the synthesis of levamisole in high optical yield. The chiral bisphosphine is obtained by reacting a chiral enantiomer of trans-2,3-bis(diphenylphosphinomethyl)bicyclo[2.2.1]heptane with a rhodium complex.
U.S. Pat. No. 4,440,936 to Riley describes a chiral phosphine ligand which when complexed with rhodium functions as a superior chiral hydrogenation catalyst. The chiral phosphine ligand component of the catalyst is formed in a four-step process that finally results in the formation of a cyclohexyl-containing phosphine which provides a yield of about 30%.
U.S. Pat. No. 4,654,176 to Dang et al. discloses novel sulfonated chiral phosphines which in many embodiments includes a cycloalkyl constituent. These phosphines are obtained by the sulfonation of a phosphine substituted with an aryl group and two straight, branched or cyclic alkyls, one of which is chiral.
U.S. Pat. No. 5,021,593 to Nohira et al. sets forth a ruthenium-containing optically active phosphine complex which includes the ligand 2,2'-bis(dicyclohexylphosphino)-6,6'-dimethyl-1,1'-biphenyl (BICHEP). The BICHEP ligand is prepared in a complex process involving 13 steps.
Of interest in the process of this invention is the paper, Chesnut et al., Organometallics, 10, 321-328 (October, 1991). This paper sets forth a method for making a class of niobium and tantalum aryloxides. The metal aryloxides are characterized by NMR spectropscopy.
There are additional processes known in the art for making cycloalkyl substituted phosphines. However, the last mentioned Nohiro et al. patent illustrates the complexity of these processes and the strong need in the art for simpler and effective methods of forming cycloalkyl-substituted phosphine ligands useful in the formation of transition metal-containing optically active complexes useful in the catalytic formation of important chiral compounds.